|
|
Blood, 1 March 2005, Vol. 105, No. 5, pp. 1881-1890.
Prepublished online as a Blood First Edition Paper on September 9, 2004; DOI 10.1182/blood-2003-12-4420.
 Previous Article | Next Article 
Submitted December 30, 2003
Accepted August 26, 2004
Molecular Analysis of a Large Cohort of Patients with the Hyper IgM Syndrome (HIGM)
Wen-I Lee, Troy R Torgerson, Michael J Schumacher, Leman Yel, Qili Zhu, and Hans D Ochs*
Department of Pediatrics, University of Washington, School of Medicine, Seattle, WA, USA; Department of Pediatrics, Chang Gung Children's Hospital & Graduate Institute of Clinical Medical Sciences, Chang Gung University, Kwei-Shan Hsiang, Taoyuan, Taiwan
Department of Pediatrics, University of Washington, School of Medicine, Seattle, WA, USA
Department of Pediatrics and Medicine, University of Arizona, Tucson, AZ, USA
Department of Medicine, University of California, Irvine, CA, USA
* Corresponding author; email: allgau{at}u.washington.edu.
The Hyper IgM syndrome (HIGM), characterized by recurrent infections, low serum IgG and IgA, normal or elevated IgM, and defective class switch recombination and somatic hypermutation, is a heterogenous disorder with at least five distinct molecular defects, including mutations of the genes coding for CD40 ligand (CD40L) and IKK-gamma (NEMO) genes, both X-linked; and mutations of CD40, Activation-Induced Cytidine Deaminase (AICDA), and Uracil-DNA Glycosylase (UNG), associated with autosomal recessive HIGM syndromes.
To investigate the molecular basis of HIGM, we determined the prevalence of mutations affecting these five genes in a cohort of 140 patients (130 males/10 females). Those without a molecular diagnosis were subsequently evaluated for mutations of the following genes: Inducible CO-Stimulator molecule (ICOS), ICOS ligand (ICOSL), and if male, Bruton's tyrosine kinase (Btk) and SLAM-associated protein (SAP/SH2D1A). We found mutations of CD40L in 98 males; AICDA in 4 patients (3 males, 1 female); UNG in one adult male; and Btk in 3 boys. Of the remaining 25 males, one infant with hypohidrotic ectodermal dysplasia had a mutation of NEMO. None of the remaining 33 patients (24 males/9 females) had mutations affecting CD40, ICOS, ICOSL or SAP, and are best classified as common variable immune deficiency (CVID), although other genes, including some not yet identified, may be responsible.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Herve, I. Isnardi, Y.-s. Ng, J. B. Bussel, H. D. Ochs, C. Cunningham-Rundles, and E. Meffre
CD40 ligand and MHC class II expression are essential for human peripheral B cell tolerance
J. Exp. Med.,
July 9, 2007;
204(7):
1583 - 1593.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Erdos, K. Alapi, and L. Marodi
Retrospective diagnosis of X-linked hyper-IgM syndrome in a family with multiple deaths of affected males
Haematologica,
February 1, 2007;
92(2):
281 - 282.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Huston
Update in allergy and immunology.
Ann Intern Med,
September 19, 2006;
145(6):
454 - 458.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Warnatz, L. Bossaller, U. Salzer, A. Skrabl-Baumgartner, W. Schwinger, M. van der Burg, J. J. M. van Dongen, M. Orlowska-Volk, R. Knoth, A. Durandy, et al.
Human ICOS deficiency abrogates the germinal center reaction and provides a monogenic model for common variable immunodeficiency
Blood,
April 15, 2006;
107(8):
3045 - 3052.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
